Age-sensitive T cell phenotypes covary in genetically heterogeneous mice and predict early death from lymphoma.
We have assessed several age-sensitive indicators of immune status in young (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see if these varied in parallel and to determine if one or more of the status indices predicted life span or cancer incidence. We report that the number of memory (i.e., CD44hi) T cells within the CD8 subset is correlated with number of memory cells in the CD4 population, and inversely correlated with the number of naive (i.e., CD45RBhi) CD4 cells at both 6 and 11 months of age, suggesting that the conversion of naive to memory cells may occur at similar rates in both T cell subsets. Mice that ranked high in the proportion of memory T cells (within the CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11 months, suggesting that the pace or extent of memory cell formation may be a consistent trait that distinguishes mice at least within a genetically heterogeneous population. Mice that at 6 months of age exhibited high levels of CD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T cells able to proliferate in response to Con A and IL-2 were found to be significantly more likely than their littermates to die within the first 18 months of life. Cases of follicular cell lymphoma, lymphocytic and lymphoblastic lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at early ages.(ABSTRACT TRUNCATED AT 250 WORDS)
Miller
R A
RA
Department of Pathology, University of Michigan.
Turke
P
P
Chrisp
C
C
Ruger
J
J
Luciano
A
A
Peterson
J
J
Chalmers
K
K
Gorgas
G
G
VanCise
S
S
D000375:Aging / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D002423:Cause of Death; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D018960:Hyaluronan Receptors; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D008136:Longevity; D008213:Lymphocyte Activation / Q000276:immunology; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D003208:Concanavalin A