Abstract
This study examined the naive and memory phenotypic profiles of CD4+ and CD8hi T cells that were mobilized to the peripheral circulation during a combination of
aerobic exercise and heat stress, determining expression of the adhesion molecules
CD62L and CD11a on the recruited cells. Twelve recreationally active males (age 27.1
± 5.3 yr, height 1.77 ± 0.08 m, mass 76.9 ± 12.0 kg, V˙O2peak 43.9 ± 6.7 mL × kg-1 × min-1) completed a 40 min bout of cycle ergometry at 65 % of V˙O2peak while immersed to mid-chest in a water bath at 39 °C. Venous blood samples were
collected before (T0), during (T40) and 30 min after (T70) exposure to combined exercise and heat stress. Specimens were analyzed by three-colour
flow cytometry for CD4+ and CD8hi T cell expression of CD45RO, CD11a and CD62L. Some 80 % of the CD4+ T cells that were mobilized were of the CD45RO memory phenotype, with the numbers
of CD11alo and CD62L+ cells increasing more than those of CD11ahi and CD62L- cells. For the CD8hi cells, there was a more equal recruitment of CD45RO- naive (43 %) and CD45RO+ memory (57 %) cells. The majority (84 %) of recruited CD8+ cells were CD11ahi; there was a trend to predominance of CD62L- cells (57 %) for the memory subset, but with almost equal recruitment of CD62L+/- for the naive subset. We conclude that the exercise + heat stress induced trend to
an increase in CD4+ T cells is linked in some way to memory phenotype; it cannot be explained simply
by a high density expression of CD11a and lack of the lymph node homing receptor (CD62L).
Furthermore, although mobilization of CD8hi T cells is not linked to memory phenotype, a high density expression of CD11a and
a lack of the lymph node homing receptor are important determinants of CD8hi T cell mobilization.
Key words
Adhesion molecules - exercise immunology - lymphocyte mobilization - anti-inflammatory
T cells
References
- 1
Akbar A N, Terry L, Timms A, Beverley C L, Janossy G.
Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells.
J Immunol.
1988;
140
2171-2178
- 2
Austrup F, Vestweber D, Borges E, Lohning M, Brauers R, Herz U.
P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into
inflamed tissues.
Nature .
1997;
385
81-83
- 3
Bell E B, Sparshott S M.
Interconversion of CD45R subsets of CD4 T cell in vivo.
Nature .
1990;
348
163-166
- 4
Berg M, Murakawa Y, Camerini D, James S P.
Lamina propria lymphocytes are derived from circulating cells that lack the Leu-8
lymph node homing receptor.
Gasteroenterol.
1991;
101
90-99
- 5
Bottomly K.
A functional dichotomy in CD4+ T lymphocytes.
Immunol Today.
1988;
9
268-274
- 6
Brenner I KM, Shek P N, Shephard R J.
Heat exposure and immune function: Potential contributions to the immune response.
Exerc Immunol Rev.
1995;
1
49-80
- 7
Butcher E C, Picker L J.
Lymphocyte homing and homeostasis.
Science.
1996;
272
60-66
- 8
Byrne J A, Butler J L, Cooper M D.
Differential activation requirements for virgin and memory T cells.
J Immunol.
1988;
141
3249-3257
- 9
Clement L, Yamashita N, Martin A.
The functionally distinct subpopulations of human CD4+ helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially
from a differentiation pathway that is regulated by activation-dependent post-thymic
differentiation.
J Immunol.
1988;
141
1464-1470
- 10
Constant S L, Bottomly K.
Induction of TH1 and TH2 CD4+ T cell responses: The alternative approaches.
Ann Rev Immunol.
1997;
15
297-322
- 11
De Jong R, Brouwer M, Miedema F, Van Lier R AW.
Human CD8+ T lymphocytes can be divided into CD45RA+ and CD45RO+ cells with different requirements for activation and differentiation.
J Immunol.
1991;
146
2088-2094
- 12
Dhabhar F S, Miller A H, McEwen B S, Spencer R L.
Effects of stress on immune cell distribution: dynamics and hormonal mechanisms.
J Immunol.
1995;
154
5511-5527
- 13
Dill D B, Costill D L.
Calculation of percentage changes in volumes of blood, plasma and red cells in dehydration.
J Appl Physiol.
1974;
37
247-248
- 14
Foster N K, Martyn J B, Rangno R E, Hogg J C, Pardy R L.
Leukocytosis of exercise: role of cardiac output and catecholamines.
J Appl Physiol.
1986;
61
2218-2223
- 15
Fujii Y, Okumura M, Inada K, Nakahara K.
Reversal of CD45 isoform switching in CD8+ T cells.
Cell Immunol.
1992;
139
176-184
- 16
Gabriel H, Kindermann W.
Flow cytometry: principles and applications in exercise immunology.
Sports Med.
1995;
20
302-320
- 17
Gabriel H, Schmitt B, Urhausen A, Kindermann W.
Increased CD45RA+CD45RO+ cells indicate activated T cells after endurance exercise.
Med Sci Sports Exerc.
1993;
25
1352-1357
- 18
Gabriel H, Schwarz L, Born P, Kindermann W.
Differential mobilization of leukocyte and lymphocyte subpopulations into the circulation
during endurance exercise.
Eur J Appl Physiol.
1992;
65
529-534
- 19
Gabriel H, Urhausen A, Kindermann W.
Circulating leucocyte and lymphocyte subpopulations before and after intensive endurance
exercise to exhaustion.
Eur J Appl Physiol.
1991;
63
449-457
- 20
Gallatin M, John T PS, Siegelman M, Reichart R, Butcher E C, Weissman I L.
Lymphocyte homing receptors.
Cell.
1985;
44
673-680
- 21
Gallatin W M, Weissman I L, Butcher E C.
A cell-surface molecule involved in organ-specific homing of lymphocytes.
Nature.
1983;
304
30-34
- 22
Gannon G A, Rhind S G, Shek P N, Shephard R J.
Differential cell adhesion molecule expression and lymphocyte mobilisation during
prolonged aerobic exercise.
Eur J Appl Physiol.
2001;
84
272-282
- 23
Jung T M, Gallatin W M, Weissman I L, Dailey M O.
Down-regulation of homing receptors after T cell activation.
J Immunol.
1988;
141
4110-4117
- 24
Kanegane H, Kasahara Y, Niida Y, Yachie A, Sughii S, Takatsu K, Taniguchi N, Miyawaki T.
Expression of L-selectin (CD62L) discriminates Th1 and Th2-like cytokine-producing
memory CD4+ T cells.
Immunol.
1996;
87
186-190
- 25
Klonz A, Wonigeit K, Pabst R, Westermann J.
The marginal blood pool of the rat contains not only granulocytes, but also lymphocytes,
NK cells and monocytes: a second intravascular compartment, its cellular composition,
adhesion molecule expression and interaction with the peripheral blood pool.
Scand J Immunol.
1996;
44
461-469
- 26
Kurokawa Y, Shinkai S, Torii J, Hino S, Shek P N.
Exercise-induced changes in the expression of surface adhesion molecules on circulating
granulocytes and lymphocyte subpopulations.
Eur J Appl Physiol.
1995;
71
245-252
- 27
Landay A L, Muirhead K A.
Procedural guidelines for performing immunophenotyping by flow cytometry.
Clin Immunol Immupathol.
1989;
52
48-60
- 28
Lanier L L, Phillips J H, Hackett J, Tutt M, Kumar V.
Natural killer cells: definition of a cell type rather than function.
J Immunol.
1986;
137
2735-2739
- 29
Mackay C R.
Homing of naive, memory and effector lymphocytes.
Curr Opin Immunol.
1993;
5
423-427
- 30
Mackay C R, Marston W L, Dudler L.
Naive and memory T cells show distinct pathways of lymphocyte recirculation.
J Exp Med.
1990;
171
801-817
- 31
Mosmann T R, Coffman R L.
Heterogeneity of cytokine secretion patterns and functions of helper T cells.
Adv Immunol.
1989;
46
111-147
- 32
Mosmann T R, Sad S.
The expanding universe of T-cell subsets: Th1, Th2 and more.
Immunol Today.
1996;
17
138-146
- 33
Okumura M, Fujii Y, Inada K, Nakahara K, Matsuda H.
Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1
expression, a phenotype of primed T cells.
J Immunol.
1993;
150
429-437
- 34
Oppenheimer-Marks N, Davis L, Lipsky P E.
Human T lymphocyte adhesion to endothelial cells and transendothelial migration.
J Immunol.
1990;
145
140-148
- 35
Pabst R, Binns R M.
Heterogeneity of lymphocyte homing physiology: Several mechanisms operate in the control
of migration to lymphoid and non-lymphoid organs in vivo.
Immunological Reviews.
1989;
108
83-109
- 36
Picker L, Treer J, Ferguson-Darnell B, Collins P, Bergstresser P, Terstappen L.
Control of lymphocyte recirculation in man: 2. Diffferential regulation of the cutaneous
lymphocyte-associated antigen, a tissue selective homing receptor for skin-homing
T-cells.
J Immunol.
1993;
150
1122-1136
- 37
Picker L, Treer J, Ferguson-Darnell B, Collins P, Buck D, Terstappen L.
Control of lymphocyte recirculation in man. 1. Differential regulation of the peripheral
lymph node homing receptor L-selectin on T cells during the virgin to memory cell
transition.
J Immunol.
1993;
150
1105-1121
- 38
Picker L J, Terstappen L W, Rott L S, Streeter P R, Stein H, Butcher E C.
Differential expression of homing-associated adhesion molecules by T cell subsets
in man.
J Immunol.
1990;
145
3247-3255
- 39
Prince H E, York J, Jensen E R.
Phenotypic comparison of the three populations of human lymphocytes defined by CD45RO
and CD45RA expression.
Cell Immunol.
1992;
145
254-262
- 40
Rhind S G, Gannon G A, Shek P N, Brenner I KM, Zamecnik J, Buguet A, Natale V M, Shephard R J,
Radomski M W.
Contribution of exertional hyperthermia to sympathoadrenal-mediated lymphocyte subset
redistribution.
J Appl Physiol.
1999;
87
1178-1185
- 41
Romagnani S.
The Th1/Th2 paradigm.
Immunol Today.
1997;
18
263-267
- 42
Sallusto F, Mackay C R, Lanzavecchia A.
Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells.
Science.
1997;
277
2005-2007
- 43
Saltini C, Trapnell B C, Tamura N, Crystal R G.
Biased accumulation of T lymphocytes with ‘memory'-type CD45 leucocyte common antigen
gene expression on the epithelial surface of the human lung.
J Exp Med.
1990;
171
1123-1140
- 44
Sanders M E, Makgoba M W, Sharrow S O, Stephany D, Springer T A, Shaw S.
Human memory T lymphocytes express increased levels of three cell adhesion molecules
(LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have
enhanced IFN-gamma production.
J Immunol.
1988;
140
1401-1407
- 45
Schweighoffer T, Tanaka Y, Tidswell M, Erle D J, Horgan K J, Ginther Luce G E, Lazarovits A I,
Buck D, Shaw S.
Selective expression of integrin alpha-4 beta-7 on a subset of human CD4+ memory T
cells with hallmarks of gut-trophism.
J Immunol.
1993;
151
717-729
- 46
Stamper H B, Woodruff J J.
Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity
of recirculating lymphocytes for high endothelial venules.
J Exp Med.
1976;
144
828-833
- 47
Tedder T F, Penta A C, Levine H B, Freedman A S.
Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and
Leu-8 differentiation antigens.
J Immunol.
1990;
144
532-540
- 48
Tsuji T, Nibu R, Iwai K, Kanegane H, Yachie A, Seki H, Miyawaki T, Tanaguchi N.
Efficient induction of immunoglobulin production in neonatal naive B cells by memory
CD4+ T cell subset expressing homing receptor L-selectin.
J Immunol.
1994;
152
4417-4424
- 49
Yamashita N, Clement L T.
Phenotypic characterization of the post-thymic differentiation of human alloantigen-specific
CD8+ cytotoxic T lymphocytes.
J Immunol.
1989;
143
1518-1523
- 50
Youseffi-Etemad R, Axelsson B.
Parallel pattern of expression of CD43 and of LFA-1 on the CD45RA+ (naive) and CD45RO+ (memory) subsets of human CD4+ and CD8+ cells. Correlation with the aggregative response of the cells to CD43 monoclonal
antibodies.
Immunol.
1996;
87
439-446
Prof. R. J. Shephard
PO Box 521 · 41390 · Dryden Rd. · Brackendale · BC · V0N 1H0 · Canada
Phone: +1 (604) 8985527
Fax: +1 (604) 8985724
Email: royjshep@shaw.ca