Requirements for CD4(+) T cell levels in acute Mycobacterium bovis strain bacille Calmette Guerin (BCG)-induced granulomas differ for optimal mycobacterial control versus granuloma formation.
Bacille Calmette Guérin (BCG)-induced granulomas contain T cells that express a broad TCR repertoire even at the level of the individual lesion. We have developed a BCG infection model in mice having only one T cell specific for a recombinant BCG epitope expressed in a lipoprotein fusion protein. Here we report that the single T cell model induces well-formed granulomas, but has weaker protection than that conferred by wild-type granulomas. This finding correlates with lower CD4(+) T cell recruitment into acute granulomas (3 weeks post infection). Chronic granulomas (6 weeks post infection) contain similar proportions of CD4(+) T cells in both models, but in the single T cell model the proportion of leukocyte function-associated antigen-1 low, non-IFNgamma-producing CD4(+) T cells is lower. In fact, even though it is likely that there are very few, if any, IFNgamma(+) CD4(+) T cells present in the single T cell model, granuloma integrity is not influenced, indicating that high levels of IFNgamma are not required for granuloma maintenance. These data underline the importance of early CD4(+) T cell recruitment into the granuloma to anti-mycobacterial protection and show that CD4(+) T cell levels required for granuloma formation and optimal protection are different. These data also show that T cell repertoire complexity contributes to protection against mycobacteria.
Hogan
Laura H
LH
University of Wisconsin School of Medicine and Public Health, Pathology and Laboratory Medicine, 5468 Medical Science Center, 1300 University Avenue, Madison, WI 53705, USA. msandor@wisc.edu
Heninger
Erika
E
Elsner
Rebecca A
RA
Vonderheid
Heidi A
HA
Hulseberg
Paul
P
Co
Dominic
D
Sandor
Matyas
M
D000208:Acute Disease; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009164:Mycobacterium Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D009163:Mycobacterium bovis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D001500:BCG Vaccine; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell