Accumulation and local proliferation of antigen-specific CD4+ T cells in antigen-bearing tissue.
Although activation and subsequent expansion of naive CD4(+) T cells within lymph nodes is well characterized, the fate of T effector cells activated within peripheral tissues during secondary reactions is poorly defined. Therefore, we studied the recruitment, proliferation and egress of antigen-specific Th1 effector cells in comparison with nonspecific Th1 cells throughout a delayed-type hypersensitivity reaction (DTH). Although we observed a high turnover of Th1 effector cells with unspecific high-rate recruitment and CCR7-dependent egress from the inflamed tissue in the early, acute DTH phase, a strong, selective accumulation of antigen-specific T cells occurred during the chronic, late DTH phase. This was mainly based on local proliferation of CD4(+) effector cells within the DTH tissue and concomitant retention. Considering the strong CCR7-dependent Th cell egress found in this model, the reduced CCR7 expression on antigen-specific T cells isolated from late-phase DTH tissue most likely contributes to the retention of these cells within the tissue. Thus, peripheral tissues can support not only the proliferation of CD8(+) T cells, as recently shown, but also that of CD4(+) T effector cells, forming a pool of tissue-resident T cells.
Experimentelle Rheumatologie c/o Deutsches Rheumaforschungszentrum, Charité-Universitaetsmedizin, Berlin, Germany.
Cornelia
C
Doebis
Astrid
A
Menning
Katrin
K
Neumann
Saeed
S
Ghani
Kerstin
K
Schlawe
Uta
U
Lauer
Alf
A
Hamann
Jochen
J
Huehn
Uta
U
Syrbe
D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D054400:Receptors, CCR7 / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D054400:Receptors, CCR7