Studies of concanavalin A in nonobese diabetic mice. II. Lymphocyte tracking and phenotype responses.
We studied the tracking of 51chromium-labeled (resting) and Con A-induced (activated) tritiated thymidine-labeled syngeneic lymphocytes to adrenal, blood, brain, heart, liver, lymph nodes, pancreas, spleen, testis/ovary, thymus and thyroid in prediabetic, nonobese diabetic (NOD) mice and in age- and sex-matched C57BL/6 mice. 51Chromium-labeled cells showed no significant difference between strains in tracking to any tissue except lymph nodes (decreased in NOD vs. C57, P less than .05). Con A incubation resulted in no difference between strains in lymphocyte tracking to lymph nodes, but NOD mice had increased pancreatic tracking with Con A-incubated cells compared to C57 mice (P less than .05). Female NOD mice had reduced thymic tracking (P = .001) compared to C57 controls. Positive selection experiments showed the Con A-responsive cell to be a T cell. Both Lyt2+ (CD8+) and L3T4+ (CD4+) enriched T cell populations showed a labeling response to Con A. After 48 h of Con A incubation, the L3T4+/Lyt2+ ratio increased in splenocytes from NOD mice (P less than .05), whereas it decreased in C57 controls (P less than .01). Over the course of 6 days in culture, NOD splenocytes exposed to Con A characteristically exhibited a delayed expansion of the Lyt2+ population. We conclude that Con A incubation of NOD splenocytes results in T cells that, when reinfused, avoid the thymus and track preferentially to the pancreas. Con A immunomodulation as potential treatment for autoimmune disease warrants further study in this murine model.
Mukherjee
B
B
Sansum Medical Research Foundation, Santa Barabara, California.
Pearce
R B
RB
Formby
B
B
Peterson
C M
CM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D002465:Cell Movement; D003208:Concanavalin A / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D013045:Species Specificity
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D003208:Concanavalin A